Takeshi Tsuruda, Makoto Ebine, Aya Umeda, Tohru Oishi, Stereoselective Synthesis of the C1-C29 Part of Amphidinol 3., J. Org. Chem., 10.1021/jo502322m, 80, 2, 859–871, 2015.01, Stereoselective synthesis of the C1-C29 part of amphidinol 3 (AM3) was achieved. The C1-C20 part was assembled from three building blocks via regioselective cross metathesis to form the C4-C5 double bond, and addition of an alkenyllithium and a lithium acetylide to two Weinreb amides followed by asymmetric reduction to form the C9-C10 and C14-C15 bonds, respectively. The C21-C29 part was synthesized via successive cross metathesis and oxa-Michael addition sequence to construct the 1,3-diol system at C25 and C27, and Brown asymmetric crotylation to introduce the stereogenic centers at C23 and C24. Coupling of the C1-C20 and C21-C29 parts was achieved by Julia-Kocienski olefination, and regio- and stereoselective dihydroxylation of the C20-C21 double bond in the presence of the C4-C5 and C8-C9 double bonds to afford the C1-C29 part of AM3..

2.

Hisaaki Onoue, Tomomi Baba, Keiichi Konoki, Kohei TORIKAI, Makoto EBINE, Tohru Oishi, Synthesis and Biological Activity of the QRS Ring System of Maitotoxin. , Chem. Lett., 10.1246/cl.140789, 43, 12, 1904-1906, 2014.09, Maitotoxin (MTX) is a ladder-shaped polyether produced by an epiphytic dinoflagellate. As a part of our structure-activity relationship studies using synthetic partial structures of MTX, the QRS ring comprised of a 6/6/7 tricyclic system was synthesized through stereoselective construction of the five contiguous stereogenic centers on the Q ring via i) coupling of a Weinreb amide and a furyllithium, followed by ii) Noyori asymmetric transfer hydrogenation, iii) Achmatowicz reaction, iv) chemoselective methylation of a methyl acetal in the presence of a carbonyl group by treatment with Me2Zn/BF3·OEt2, v) highly diastereoselective dihydroxylation, and vi) ring expansion of a six-membered to a seven-membered ring ketone. The synthetic specimen inhibited MTX-induced Ca2+ influx with an IC50 value of 44 microM..

3.

Masahiro Kunitake, Takahiro Oshima, Keiichi Konoki, Michio Murata, Tohru Oishi, Synthesis and Biological Activity of the C’D’E’F’ Ring System of Maitotoxin. , J. Org. Chem. , 10.1021/jo5005235, 79, 11, 4948-4962, 2014.03, Stereoselective synthesis of the C’D’E’F’ ring system of maitotoxin was achieved starting from the E’ ring through successive formation of the D’ and C’ rings based on SmI2-mediated reductive cyclization. Construction of the F’ ring was accomplished via Suzuki-Miyaura cross coupling with a side chain fragment and Pd(II)-catalyzed cyclization of an allylic alcohol. The C’D’E’F’ ring system inhibited MTX-induced Ca2+ influx in rat glioma C6 cells with an IC50 value of 59 microM.

4.

Tohru Oishi, Keiichi Konoki, Masahiro Kunitake, Rie Tamate, Kohei TORIKAI, Futoshi Hasegawa, Nobuaki Matsumori, Michio Murata, Artificial ladder−shaped polyethers that inhibit maitotoxin−induced Ca2+ influx in rat glioma C6 cells. , Bioorg. Med. Chem. Lett., 10.1016/j.bmcl.2012.04.053, 22, 11, 3619−3622, 2012.06, Maitotoxin (MTX) is a ladder-​shaped polyether produced by the epiphytic dinoflagellate Gambierdiscus toxicus. It is known to elicit potent toxicity against mammals and induce influx of Ca2+ into cells. An artificial ladder-​shaped polyether possessing a 6​/7​/6​/6​/7​/6​/6 heptacyclic ring system, which was designed for elucidating interactions with transmembrane proteins, was found to be the most potent inhibitor against MTX-​induced Ca2+ influx that has ever been reported. .